NAD-Dependent HDAC Modulators

Although the localisation patterns of some of the Sirtuins (class III HDACs) and their unique NAD-dependent deacetylation mechanism are known [58], less is understood about their functions and targets when compared to other HDACs [59]. The field of small molecule Sirtuin modulators is also correspondingly less advanced, because this alternative mechanism renders the zinc-dependent 

A large number of patent applications has been filed, most recently describing imidazothiazoles [70], oxazolopyridines [71], benzimidazoles [72], benzothiazoles [73] and imidazopyridines [74] as sirtuin modulators, however it is not yet possible to determine which compound classes will prove most promising. Overall, due to their potential applications as new drug candidates for various indications, the class III HDAC inhibitors are currently a rapidly growing field of interest. 

Bacterial resistance to antibiotics is an emerging public health crisis. The prevalence of pathogens resistant to currently available antibiotics continues to grow annually. Two million patients in the U.S. acquire an infection during a hospital stay and approximately 90,000 of these patients die each year as a result of the infection [1]. More than 70% of hospital-acquired infections are now resistant to 

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Annual Reports in Medicinal Chemistry, Volume 42 ISSN 0065-7743, DOI 10.1016/S0065-7743(07)42022-X 

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